Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease.

The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer's disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3×Tg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD.

Low-dose of magnesium sulfate solution was not inferior to standard regime of polyethylene glycol for bowel preparation in elderly patients: a randomized, controlled study.

BACKGROUND: Large polyethylene glycol (PEG) is a standard regimen for bowel preparation. However, elderly patients suffered from adverse events. This study was to compare the efficacy and safety of oral magnesium sulfate solution (MSS) vs standard PEG in elderly patients undergoing colonoscopy. METHODS: Elderly patients aged 60-90 years, from two endoscopic centers, were enrolled in China. Patients were randomized to take a low dose of MSS or a standard PEG regime in a split-dose regime. The primary endpoint was the proportion of patients with adequate bowel preparation, which was defined as the total Boston Bowel Preparation Scale (BBPS) ≥6 and each segmental BBPS was ≥2. Secondary outcomes included adenoma detection rate (ADR), safety, adverse events, cecal intubation rate, willingness to repeat BP, and so on. RESULTS: 1174 elderly patients were randomly allocated to the MSS group (n = 588) or the standard group (n = 586). Adequate BP was achieved in 94.0% of patients in the MSS group and 92.5% in the control (p = .287). ADR was also comparable between the two groups (43.0% and 39.9%, p = .282). Compared with the standard group, MSS group reported less abdominal discomfort (1.7% vs 6.0%), less nausea (13.6% vs 21.0%) and vomiting (1.2% vs 4.2%). The change in serum potassium levels after preparation in the standard group was significantly lower than that in the MSS group (-0.19 ± 0.08 vs -0.41 ± 0.11, p = .037). CONCLUSIONS: Low dose of MSS was not inferior to the standard PEG regime in terms of bowel preparation quality for elderly patients. Low-dose MSS offered fewer adverse events and better tolerability. It is a preferable choice for the elderly to undergo bowel preparation for colonoscopy. CLINICAL TRIAL REGISTRATION NUMBER: NCT04948567.

Rapid detection of Chinese-specific peony seed oil by using confocal Raman spectroscopy and chemometrics.

Peony seed oil (PSO) is a new woody nut oil which is unique to China. Its unsaturated fatty acids are over 90% and are rich in α - linolenic acid. Although the PSO industry is in its infancy, it is bound to become a top vegetable oil food material because of its own advantages. The potential high commercial profit of its adulteration with cheap vegetable oil will be an important factor hindering the healthy development of PSO industry. It is of great significance to study the adulteration of PSO for preventing large-scale adulteration. In this study, the qualitative and quantitative analysis of PSO was realised based on Raman spectroscopy combined with chemometrics analysis, and the fatty acid composition of PSO was analysed according to Raman characteristic peaks. The technology can be applied to routine analysis and quality control of PSO.

TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO.

Sensing of pathogenic nucleic acids by pattern recognition receptors (PRR) not only initiates anti-microbe defense but causes inflammatory and autoimmune diseases. E3 ubiquitin ligase(s) critical in innate response need to be further identified. Here we report that the tripartite motif-containing E3 ubiquitin ligase TRIM41 is required to innate antiviral response through facilitating pathogenic nucleic acids-triggered signaling pathway. TRIM41 deficiency impairs the production of inflammatory cytokines and type I interferons in macrophages after transfection with nucleic acid-mimics and infection with both DNA and RNA viruses. In vivo, TRIM41 deficiency leads to impaired innate response against viruses. Mechanistically, TRIM41 directly interacts with BCL10 (B cell lymphoma 10), a core component of CARD proteins-BCL10 - MALT1 (CBM) complex, and modifies the Lys63-linked polyubiquitylation of BCL10, which, in turn, hubs NEMO for activation of NF-κB and TANK-binding kinase 1 (TBK1) - interferon regulatory factor 3 (IRF3) pathways. Our study suggests that TRIM41 is the potential universal E3 ubiquitin ligase responsible for Lys63 linkage of BCL10 during innate antiviral response, adding new insight into the molecular mechanism for the control of innate antiviral response.

Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome.

Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

Exosomal-lncRNA DLEU1 Accelerates the Proliferation, Migration, and Invasion of Endometrial Carcinoma Cells by Regulating microRNA-E2F3.

PURPOSE: Long non-coding RNAs (lncRNAs) may act as oncogenes in several cancers, including endometrial carcinoma (EC). The purpose of the current study is to investigate the regulatory mechanism of exosomal-lncRNA deleted in lymphocytic leukemia1 (DLEU1) on EC. METHODS: The expression levels of lncRNA DLEU1, microRNA-381-3p and E2F Transcription Factor 3 (E2F3) in EC tissues or cells were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We then analysed the proliferation, migration, and invasion of EC cells by performing the MTT assay, wound healing assay, and transwell invasion assay, respectively. Identification of exosomes was detected using Western blot assay. The uptake of exosomes was detected by a confocal microscope. The effects of exosomes on EC cells were investigated by construction of cell co-culture system. The interactions among DLEU1, miR-381-3p and E2F3 were confirmed using the dual-luciferase reporter (DLR) assay. RESULTS: LncRNA DLEU1 expression was highly up-regulated in EC tissues and cells. Knockdown of DLEU1 inhibited the proliferation, migration, and invasion of EC cells. Exosomes could be uptaken by the ambient EC cells. MiR-381-3p was a target of DLEU1 and was negatively modulated by DLEU1. Overexpression of miR-381-3p suppressed the proliferation, migration, and invasion of EC cells. Additionally, E2F3 was the target gene of miR-381-3p and was negatively modulated by miR-381-3p. Upregulation of miR-381-3p and down-regulation of E2F3 reversed the promoting effect of exosomal DLEU1 on EC cells. CONCLUSION: Exosomal DLEU1 accelerates the development of EC by regulating the miR-381-3p/E2F3 axis, thus DLEU1 may act as a possible therapeutic target for treating EC.

Iron-Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta-Catenin Signaling.

BACKGROUND: The incidence of osteoporotic fractures is increasing. In this study, we explored the activities of Wnt/ß-catenin signaling in bone tissues with iron accumulation. METHODS: We established rat bipedal walking models (RBWM), and a portion of our RBWM rats were intraperitoneally injected with ferric ammonium citrate, normal saline, and deferoxamine. Bone mineral density was measured with a small animal in vivo imaging system. The protein levels of ferritin, TRAP-5B, RANKL, and OPG in serum were measured by the enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify the RNA and protein expression levels of certain regulators involved in Wnt/ß-catenin signaling in bone tissues. RESULTS: In the present study, we established a rat bipedal walking model containing 32 bipedal rats, which were randomly classified into four groups, termed as NS, FAC, FAC+NS, and FAC+DFO. Those three experimental groups with FAC injection had significantly lower bone mineral density (BMD) than the control group NS (P < 0.05). The disruption of bone homeostasis and downregulation of Wnt/ß-catenin signaling were also observed in the three groups with FAC injection. Moreover, after the injection of deferoxamine, those aberrations in samples with FAC injection seemed repaired as test results returning or getting close to normal ranges. CONCLUSION: The osteoporosis could be caused by iron overload, which reduced the bone mineral density by disrupting the homeostasis of bone formation and absorption and attenuating the Wnt/ß-catenin signaling in bone tissues. The deferoxamine had the potential to improve the bone health by reducing the accumulation of iron and increasing the bone mass, which might be a promising therapeutic solution for osteoporosis.

MicroRNA-155 Suppresses the Translation of p38 and Impairs the Functioning of Dendritic Cells in Endometrial Cancer Mice.

BACKGROUND: Dendritic cells (DCs) are reported to play an important role in activating the anti-tumor immune responses. p38 MAPK14 signaling plays an important role in controlling their activity. Here, we identified that miR-155 suppressed the translation of p38 and impaired the functioning of dendritic cells in endometrial cancer. METHODS: HEC1A endometrial cancer cell lines were used for the study which was transfected in the C57BL/6 mice. Murine bone marrow-derived dendritic cells (BMDCs) were isolated from the mice. Target prediction was done by TargetScan which was confirmed by RT-PCR analysis. The protein expression was carried by Western blot analysis. Levels of IL-12 were evaluated by ELISA. Mice injected with HEC1A cells were subjected to tumor challenge study. RESULTS: On screening the binding sites of p38 MAPK14 gene, miR-155 was found to bind the 3'UTR directly and blocked its translation. The levels of miR-155 were upregulated in dendritic cells and RAW264.7 cells, miR-155 showed inhibitory effect on expression levels of p38. In dendritic cells, miR-155 was found to regulate the expression of IL-12, also miR-155 inhibitor stimulated the differentiation of Th1 cells in mice induced with endometrial cancer. In dendritic cells, miR-155 inhibited the expression of p38 gene and decreased their ability to interfere in tumor growth. CONCLUSION: The study concludes suppressive role of miR-155 in the process of dendritic cells mediated anti-tumor immunity, also inhibiting miR-155 provides a novel strategy for countering endometrial cancer.

4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response.

Deregulation of mRNA translation engenders many human disorders, including obesity, neurodegenerative diseases, and cancer, and is associated with pathogen infections. The role of eIF4E-dependent translational control in macrophage inflammatory responses in vivo is largely unexplored. In this study, we investigated the involvement of the translation inhibitors eIF4E-binding proteins (4E-BPs) in the regulation of macrophage inflammatory responses in vitro and in vivo. We show that the lack of 4E-BPs exacerbates inflammatory polarization of bone marrow-derived macrophages and that 4E-BP-null adipose tissue macrophages display enhanced inflammatory gene expression following exposure to a high-fat diet (HFD). The exaggerated inflammatory response in HFD-fed 4E-BP-null mice coincides with significantly higher weight gain, higher Irf8 mRNA translation, and increased expression of IRF8 in adipose tissue compared with wild-type mice. Thus, 4E-BP-dependent translational control limits, in part, the proinflammatory response during HFD. These data underscore the activity of the 4E-BP-IRF8 axis as a paramount regulatory mechanism of proinflammatory responses in adipose tissue macrophages.

Induction of an Alternative mRNA 5' Leader Enhances Translation of the Ciliopathy Gene Inpp5e and Resistance to Oncolytic Virus Infection.

Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Translational control of mRNA is an important feature of innate immunity, yet the identity of translationally regulated mRNAs functioning in host defense remains ill-defined. We report the translatomes of resistant murine "4T1" breast cancer cells infected with three of the most clinically advanced oncolytic viruses: herpes simplex virus 1, reovirus, and vaccinia virus. Common among all three infections are translationally de-repressed mRNAs, including Inpp5e, encoding an inositol 5-phosphatase that modifies lipid second messenger signaling. We find that viral infection induces the expression of an Inpp5e mRNA variant that lacks repressive upstream open reading frames (uORFs) within its 5' leader and is efficiently translated. Furthermore, we show that INPP5E contributes to antiviral immunity by altering virus attachment. These findings uncover a role for translational control through alternative 5' leader expression and assign an antiviral function to the ciliopathy gene Inpp5e.

Active-site mTOR inhibitors augment HSV1-dICP0 infection in cancer cells via dysregulated eIF4E/4E-BP axis.

Herpes Simplex Virus 1 (HSV1) is amongst the most clinically advanced oncolytic virus platforms. However, efficient and sustained viral replication within tumours is limiting. Rapamycin can stimulate HSV1 replication in cancer cells, but active-site dual mTORC1 and mTORC2 (mammalian target of rapamycin complex 1 and 2) inhibitors (asTORi) were shown to suppress the virus in normal cells. Surprisingly, using the infected cell protein 0 (ICP0)-deleted HSV1 (HSV1-dICP0), we found that asTORi markedly augment infection in cancer cells and a mouse mammary cancer xenograft. Mechanistically, asTORi repressed mRNA translation in normal cells, resulting in defective antiviral response but also inhibition of HSV1-dICP0 replication. asTORi also reduced antiviral response in cancer cells, however in contrast to normal cells, transformed cells and cells transduced to elevate the expression of eukaryotic initiation factor 4E (eIF4E) or to silence the repressors eIF4E binding proteins (4E-BPs), selectively maintained HSV1-dICP0 protein synthesis during asTORi treatment, ultimately supporting increased viral replication. Our data show that altered eIF4E/4E-BPs expression can act to promote HSV1-dICP0 infection under prolonged mTOR inhibition. Thus, pharmacoviral combination of asTORi and HSV1 can target cancer cells displaying dysregulated eIF4E/4E-BPs axis.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Suppresses iNOS Expression and Ameliorates Neural Impairment in Alzheimer's Disease Mice.

BACKGROUND: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been reported to exhibit therapeutic effects in various animal models of neurological diseases, such as stroke and hypoxic-ischemic brain injury. OBJECTIVE: The present study investigated the potential beneficial effect of MSC-derived EVs in an animal model of Alzheimer's disease (AD). METHODS: APP/PS1 mice and their non-transgenic littermates (WT) received intracerebroventricle injection of MSC-derived EVs once per two days for two weeks. Then novel object recognition and water maze tasks were carried out to measure the cognitive behaviors. Electrophysiological tests were carried out to measure hippocampal synaptic plasticity. Inducible nitric oxide synthase (iNOS) mRNA and protein levels were measured by qRT-PCR and western blotting in primary cultured neurons treated with amyloid-ß peptide (Aß) or prepared from APP/PS1 mice. RESULTS: Treatment with MSC-derived EVs alleviates exogenous Aß-induced iNOS mRNA and protein expression. In cultured primary neurons prepared from APP/PS1 pups, iNOS mRNA and protein levels were significantly reduced when treated with MSC-derived EVs. MSC-derived EVs improved cognitive behavior, rescued impairment of CA1 synaptic transmission, and long-term potentiation in APP/PS1 mice. CONCLUSION: MSC-derived EVs possessed beneficial effects in a mouse model of AD, probably by suppressing Aß induced iNOS expression.

Influenza A/Hong Kong/156/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30.

BACKGROUND: The genetic basis for avian to mammalian host switching in influenza A virus is largely unknown. The human A/HK/156/1997 (H5N1) virus that transmitted from poultry possesses NS1 gene mutations F103L + M106I that are virulence determinants in the mouse model of pneumonia; however their individual roles have not been determined. The emergent A/Shanghai/patient1/2013(H7N9)-like viruses also possess these mutations which may contribute to their virulence and ability to switch species. METHODS: NS1 mutant viruses were constructed by reverse genetics and site directed mutagenesis on human and mouse-adapted backbones. Mouse infections assessed virulence, virus yield, tissue infection, and IFN induction. NS1 protein properties were assessed for subcellular distribution, IFN antagonism (mouse and human), CPSF30 and RIG-I domain binding, host transcription (microarray); and the natural prevalence of 103L and 106I mutants was assessed. RESULTS: Each of the F103L and M106I mutations contributes additively to virulence to reduce the lethal dose by >800 and >3,200 fold respectively by mediating alveolar tissue infection with >100 fold increased infectious yields. The 106I NS1 mutant lost CPSF binding but the 103L mutant maintained binding that correlated with an increased general decrease in host gene expression in human but not mouse cells. Each mutation positively modulated the inhibition of IFN induction in mouse cells and activation of the IFN-ß promoter in human cells but not in combination in human cells indicating negative epistasis. Each of the F103L and M106I mutations restored a defect in cytoplasmic localization of H5N1 NS1 in mouse cells. Human H1N1 and H3N2 NS1 proteins bound to the CARD, helicase and RD RIG-I domains, whereas the H5N1 NS1 with the same consensus 103F and 106M mutations did not bind these domains, which was totally or partially restored by the M106I or F103L mutations respectively. CONCLUSIONS: The F103L and M106I mutations in the H5N1 NS1 protein each increased IFN antagonism and mediated interstitial pneumonia in mice that was associated with increased cytoplasmic localization and altered host factor binding. These mutations may contribute to the ability of previous HPAI H5N1 and recent LPAI H7N9 and H6N1 (NS1-103L+106M) viruses to switch hosts and cause disease in humans.

Morphological characteristics and co-stimulatory molecule (CD80, CD86, CD40) expression in tumor infiltrating dendritic cells in human endometrioid adenocarcinoma.

OBJECTIVE: The purpose of this study was to investigate changes of the antigen-presenting function of tumor infiltrating dendritic cells (TIDCs) in human endometrioid adenocarcinoma. STUDY DESIGN: The TIDCs from 45 cases of endometrioid adenocarcinoma were compared with 20 cases of normal human endometrial tissue, using transmission electron microscopic examination, and the expression of CD80, CD86, and CD40 was analyzed by flow cytometry. RESULTS: In comparison with the control group, the ultrastructure of TIDCs in human endometrioid adenocarcinoma showed the following differences: numerous TIDCs were small in volume and round in shape but some were oval and multi-angular. The cytoplasmic processes were obviously decreased in number and stubbed. Round primary lysosomes with high electron-dense granules, and secondary lysosomes with high or low electron-dense granules were seen frequently in the cytoplasm. TIDCs contained much rough endoplasmic reticulum (RER). Vacuoles with flocculent electron-dense granules were rare. High electron-dense contents in the granules were near one side and the other side was bright. The nucleus became markedly small in volume, nephroid or hoofed in shape. The nucleus had little euchromatin and lots of heterochromatin under the nuclear membrane. The levels of expression of CD80, CD86 and CD40 on TIDCs were low or even nonexistent. The expression levels of CD80, CD86 and CD40 on DCs in human normal endometrium were significantly higher than those on TIDCs in endometrioid adenocarcinoma. CONCLUSION: It is suggested that morphological differences and low expression of co-stimulatory molecules on TIDCs in endometrioid adenocarcinoma reflected the functional changes of the TIDCs in uptake, processing and presenting antigen, which may lead to the occurrence of tumor immune escape.

[Apoptosis and expression of Fas/FasL in tumor infiltrating dendritic cells in human endometrioid adenocarcinoma].

OBJECTIVE: To investigate apoptosis of tumor infiltrating dendritic cells (TIDC) and their expression of Fas/FasL (CD95/CD95L) in human endometrioid adenocarcinoma. METHODS: The apoptotic rate of TIDC was measured in 45 cases of endometrioid adenocarcinoma and 20 cases of normal endometrium tissues (control) by double-label immunohistochemistry using the monoclonal antibody S-100 protein and TUNEL technique. The expressions of Fas and FasL in TIDCs were detected using double-label immunohistochemistry and imaging analysis. RESULTS: The apoptotic rate of TIDCs in endometrioid adenocarcinoma were significantly higher than that in normal endormetrium [(13.02∓0.64)% vs (6.82∓0.53)%, P<0.05]. The expression levels of Fas in the TIDCs were significantly lower, whereas FasL expression significantly higher in endometrioid adenocarcinoma than in normal endormetrium (7.88∓1.05 vs 19.25∓3.03, P<0.05; 12.95∓2.25 vs 7.51∓1.14, P<0.05). CONCLUSION: Increased apoptosis of the TIDCs and abnormal expression of Fas/FasL in TIDCs in endometrioid adenocarcinoma may lead to tumor immune escape.

[Expression of vascular endothelial growth factor in human placental trophoblasts and angiogenesis in the chorionic villi].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) in human placental trophoblasts and the role of VEGF in regulating placental villous angiogenesis. METHODS: Placental samples were obtained from 10 pregnant women receiving induced abortion in the first trimester, 10 receiving induced labor in the second trimester and 10 having cesarean section at term delivery, with gestational duration of 6-9, 18-22 and 37-38 weeks, respectively. All the samples were fixed in formalin solution and prepared for the morphological study. The expression of VEGF and vascular distribution in the placental villi were examined and evaluated by immunohistochemistry and stereomorphometry, respectively. RESULTS: In the course of pregnancy, there was a significant decrease in the level of VEGF expression in chorionic villi (28.19+/-3.01, 18.65+/-2.43, 4.95+/-0.86, respectively, P<0.01). The radial parameters of the blood vessels showed no significant changes (26.67+/-7.74, 25.08+/-4.67, 23.36+/-5.30, respectively, P>0.05), but the length density of the blood vessels increased significantly (1.46+/-0.64, 5.58+/-1.31, 19.56+/-1.40, respectively, P<0.01). CONCLUSION: During gestation, VEGF expression in chorionic villi gradually weakens but the length density of the blood vessels increases, indicating that VEGF is not the only regulatory factor of angiogenesis in the chorionic villi.

[Effects of mifepristone on ultrastructure of placental Hofbauer cells in early human pregnancy].

OBJECTIVE: To investigate the effects of mifepristone on the ultrastructure of Hofbauer cells in human early pregnant placenta. METHODS: Twenty 6 - 9 week pregnant women with indications of pregnancy termination were recruited and randomly assigned to mifepristone group(n = 10) and D & C group (n = 10). Villi were collected and studied with transmission electron microscope. RESULTS: In comparison with the control group, the ultrastructure of Hofbauer cells of mifepristone group showed the following changes: the cells were markedly edematous. The number of cytoplasmic processes of Hofbauer cells deceased obviously. In the cytoplasm of Hofbauer cells, the size of vacuoles enlarged and of mitochondria minimized. Rough endoplasmic reticulum and Golgi complex were under-developed. Lysosomes were rare. The nuclei enlarged and showed irregular shape. CONCLUSIONS: Mifepristone may change the phagocytosis' water and electrolyte transportation and immunological function of Hofbauer cells by influencing the ultrastructure of the Hofbauer cells. Therefore it can influence the development of pregnancy.